This study aims to characterize the atypical developmental trajectory of functional brain circuitry and neurocognitive function in adolescent bipolar disorder (ABD). Our functional magnetic resonance imaging (fMRI) studies in ABD patients have found impairment in fronto-limbic and fronto-striatal circuitry. These abnormalities may underlie the affective and cognitive disturbances that are central to the illness, and have broad implication for clinical course and functional disability. To date, most studies of ABD are cross-sectional and the developmental trajectory of functional brain maturation remains poorly characterized. Therefore, we propose to extend our prior work in this area by examining the maturational trajectory of interfacing affective and cognitive brain circuitry, and to assess its impact on neurocognitive development and illness course. Our primary aim is to define the developmental changes in brain circuitry functioning in 12-14 year old recent-onset ABD patients over a three-year period during which marked changes in cognitive and affective processes are known to typically occur. The sample will include 80 newly diagnosed manic or mixed ABD patients who are stimulant and antidepressant naive, and have had no more than 4 weeks of lifetime treatment with mood stabilizers or antipsychotics. Unmedicated patients will be examined at baseline and followed subsequently on an annual basis for three years, i.e., in very early stages of disease progression, using innovative neurocognitive and fMRI paradigms to probe affective and cognitive neurocircuitry function and clinical course. A demographic and IQ matched healthy comparison group (n=80) will be studied longitudinally in parallel with the patient group. This study is innovative in its examination of the cognitive developmental and brain maturational trajectory of ABD, and will contribute to an understanding of the ways in which maturational changes in affective and cognitive neurocircuitry function deviate from normal development, and how these processes contribute to course of illness. Thus, the study will provide important information about ABD that is needed to develop more effective and neurobiologically-based early interventions, which could potentially minimize or reverse pathophysiological processes and reduce functional disability in ABD patients.

Public Health Relevance

Adolescent Bipolar Disorder (ABD) is a serious illness associated with significant affect dysregulation and cognitive dysfunction, with high rates of suicidal behavior and academic under achievement. Therefore, the proposed study aims to understand the developmental function of the interfacing affective and cognitive neural circuitry and clinical course in ABD patients, relative to a healthy comparison group, from the time of their first presentation at 12-14 years of age till they turn 15-17 years of age i.e., over a 3 year window of steep brain maturation and cognitive development. A comprehensive understanding of the "brain-behavior development and deviance from the norm" in ABD will provide future opportunities for preventive efforts by facilitating early identification, moving a step closer to safer, more effective and neurobiologically informed early interventions for youths affected by ABD.